TGF-β1 alters esophageal epithelial barrier function by attenuation of claudin-7 in eosinophilic esophagitis.
TGF-β1 alters esophageal epithelial barrier function by attenuation of claudin-7 in eosinophilic esophagitis.
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DOI：
10.1038/mi.2017.72
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发表时间：
2018-03
影响因子：
8
通讯作者：
Masterson JC
中科院分区：
文献类型：
--
作者：
Nguyen N;Fernando SD;Biette KA;Hammer JA;Capocelli KE;Kitzenberg DA;Glover LE;Colgan SP;Furuta GT;Masterson JC
屏障功能障碍与嗜酸性粒细胞性食管炎（EoE）的病理生理学有关。 TGF-β1 是一种有效的多效性分子，在 EoE 中增加，但尚无研究评估其对食管上皮屏障的影响。我们假设 TGF-β1 调节 EoE 中的屏障功能障碍。我们的目的是确定 TGF-β1 在 EoE 模型中上皮屏障中的作用。为了检查 TGF-β1 对食管屏障的影响，在体外 3 维气液界面 (3D-ALI) 模型中，将永生化人食管上皮 (EPC2-hTERT) 细胞暴露于 TGF-β1。通过跨上皮电阻 (TEER) 和 3kDa FITC 葡聚糖细胞旁通量 (FITC Flux) 测量，TGF-β1 暴露减弱了 EPC2-hTERT 屏障功能，H&E 评估显示明显的细胞分离。在上皮屏障分子的分析中，TGF-β1 导致紧密连接分子 Claudin-7 表达的特异性减少，而 TGF-β 受体 I 抑制剂可以阻止这种情况。 shRNA 介导的claudin-7 敲低会削弱上皮屏障功能，而claudin-7 过度表达则可防止TGF-β1 介导的屏障功能障碍。在儿科 EoE 活检分析中，claudin-7 表达降低，免疫荧光分析观察到定位改变，TGF-β1 下游转录因子磷酸化 SMAD2/3 (pSMAD2/3) 增加。我们的数据表明，TGF-β1 通过claudin-7 失调参与食管上皮屏障功能障碍。
Barrier dysfunction has been implicated in the pathophysiology of eosinophilic esophagitis (EoE). TGF-β1, a potent pleiotropic molecule, is increased in EoE, however, no study has evaluated its influence on esophageal epithelial barrier. We hypothesized that TGF-β1 regulates barrier dysfunction in EoE. We aimed to determine the role of TGF-β1 in epithelial barrier in models of EoE. To examine the impact of TGF-β1 on esophageal barrier, immortalized human esophageal epithelial (EPC2-hTERT) cells were exposed to TGF-β1 during the 3-dimensional air liquid interface (3D-ALI) model in vitro. TGF-β1 exposure diminished EPC2-hTERT barrier function as measured by transepithelial electrical resistance (TEER) and 3kDa FITC dextran paracellular flux (FITC Flux) and H&E assessment revealed prominent cellular separation. In analysis of epithelial barrier molecules, TGF-β1 led to the specific reduction in expression of the tight-junction molecule, claudin-7 and this was prevented by TGF-β receptor I inhibitor. shRNA mediated claudin-7 knockdown diminished epithelial barrier function, while claudin-7 overexpression resulted in protection from TGF-β1-mediated barrier dysfunction. In analysis of pediatric EoE biopsies claudin-7 expression was decreased, altered localization was observed by immunofluorescence analysis and the TGF-β1 downstream transcription factor phosphorylated SMAD2/3 (pSMAD2/3) was increased. Our data suggest that TGF-β1 participates in esophageal epithelial barrier dysfunction through claudin-7 dysregulation.
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影响因子：
14.2
作者：
Beppu, Lisa Y.;Anilkumar, Arjun A.;Newbury, Robert O.;Dohil, Ranjan;Broide, David H.;Aceves, Seema S.
通讯作者：
Aceves, Seema S.
影响因子：
3.4
作者：
Capocelli KE;Fernando SD;Menard-Katcher C;Furuta GT;Masterson JC;Wartchow EP
通讯作者：
Wartchow EP
影响因子：
3.7
作者：
Muir, Amanda B.;Lim, Diana M.;Wang, Mei-Lun
通讯作者：
Wang, Mei-Lun
DOI：
10.1152/ajplung.00349.2010
发表时间：
2012-01-01
影响因子：
4.9
作者：
Ohta, Hiromitsu;Chiba, Shigeki;Nukiwa, Toshihiro
通讯作者：
Nukiwa, Toshihiro
影响因子：
14.2
作者：
Aceves, Seema S.;Chen, Diana;Broide, David H.
通讯作者：
Broide, David H.